In separation procedures, particularly in liquid chromatography, the fluid distribution system is critical to the overall performance, and becomes more so as the cross-section of the chromatographic column increases.
Columns used in liquid chromatography typically comprise a body-forming structure enclosing a porous media through which a carrier liquid flows, with separation taking place by material distribution between the carrier liquid and solid phase of the porous media Typically, the porous media is enclosed in the column as a packed bed, typically formed by consolidating a suspension of discrete particles. An alternative to the packed bed is the so-called expanded or fluidised bed, where effective porosity and volume of the expanded bed depends on the fluid velocity. The term ‘packing’ shall be used in the following to describe the porous solid phase in both types of chromatography. The efficiency of the chromatographic separation relies in both modes strongly on the liquid distribution and collection system at the fluid inlet and outlet of the packing.
Ideally, the carrier liquid is uniformly introduced throughout the surface at the top of the packing, flows through the packing at the same velocity throughout the packing cross section, and is uniformly removed at the plane defined by the bottom of the packing.
Conventional distribution systems for use in liquid chromatography must address a number of inherent problems that have deleterious effects on the separation efficiency of the column. Among these problems are (a) non-uniform initial fluid distribution at the top of the packing as well as non-uniform fluid collection at the outlet of the packing and (b) “channelling”, which is described by a non-uniform flow field within a packing, typically caused by pressure gradients that are perpendicular to the mean direction of velocity due to pressure loss in the fluid distribution system.
With respect to the channelling problem, conventional distribution systems often rely upon the pressure drop in the distributor of a vertical chromatographic column to distribute the fluid uniformly horizontally. Whenever the pressure drop through the column is high relative to the pressure drop in the distributor, however, the fluid tends to channel in the centre of the column causing excessive dispersion. This severely limits the effectiveness of chromatographic separations and is particularly acute for large diameter columns.
The problem of non-uniform initial fluid distribution refers generally to the problem of applying a sample volume simultaneously over the cross-sectional area of the packing. Without a simultaneous introduction of fluid in the plane defined by the top of the packing, it is virtually impossible to achieve a distinct movement of a sample zone or front through the packing.
Both problems will lead to increased dispersion in the chromatographic system by broadening the convective residence time distribution of a tracer substance transported with the fluid throughout the system. The dispersion generated by the liquid distribution system has to be controlled in relation to the amount of dispersion introduced by the chromatographic packing itself by means of diffusion and mixing effects.
Standard fluid distribution systems consist of one central inlet for the mobile phase in combination with a thin distribution channel (gap) behind the filter (woven net or sinter) confining the top and bottom plane of the inlet and outlet of the packing. In theory and from experience it is known that such a system deteriorates in performance with increasing diameter of the column. This is due to the residence time difference between fluid elements travelling from the inlet to the outer column wall and those fluid elements which directly can enter the net and the packed bed region below the inlet port. This difference in residence time is enlarged with column diameter and leads to chromatographic band broadening which becomes most severe with small particles. This problem corresponds to the non-uniform initial fluid distribution.
Columns with multiple inlets have also been proposed. Multiple inlets reduce the residence time differences but are expensive to produce.
Another well-known technique for distribution is the plate system, typically utilising a plate with face openings along radii on the plate to achieve fluid distribution by decreasing the resistance of fluid flow through the plate with increasing radius. A drawback of the plate system is that the spacing and size of the openings in the plate must be calculated for any particular fluid according to its viscosity and other physical characteristics (the rheology of the fluid) so that the system will work properly with that particular fluid at a particular flow rate. A drawback to the plate system, however, is that variation in the fluid being distributed or the flow rate will affect the uniformity of the distribution.
A third technique is disclosed in U.S. Pat. No. 4,537,217, which is comprised of a layered distribution structure, comprising a first layer that acts as a cover and in which a fluid inlet is formed, a second layer wherein a number of channels are formed which each terminates in an outlet extending through the second layer. The outlets form a well-distributed pattern, which provides a high degree of fluid distribution on the packing side of the distribution system. Although this system provides excellent distribution, it suffers from several disadvantages, especially in that it is difficult to produce especially for a large number of channels at large column diameters. There is further a risk for sanitary problems due to the troublesome cleaning of such a large amount of channels of such small size, and in that it is impossible to prevent fluid from entering in between the two layers.
As a further development of the last technique, U.S. Pat. No. 5,354,460 discloses the use of a large number of fan shaped “step-down nozzles”, similar to the layered distribution structure presented above, that are arranged in concentric rings and interconnected by a manifold system. Due to the modular construction this system may be produced using large-scale production techniques, but the high grade of complexity still results in high production costs. Like the layered distribution structure, complex systems of this type are extremely difficult to clean; whereby there is an obvious risk for sanitary problems.
Another problem is that excising techniques makes it difficult to upscale from laboratory columns (small diameter) to production columns of large diameter, as it is extremely difficult to forecast the distribution characteristics. Whereby large-scale experiments have to be done to adapt laboratory processes for large-scale production to achieve an optimal process. Furthermore, it is difficult and expensive to alter the distribution characteristics of such systems.
Despite the high level of activity in the field of chromatography over many years, and the many distribution systems proposed, both speculative as well as experimentally evaluated, the need still exists for an effective, simple distribution system that will permit large liquid chromatographic columns to be used. Further there is need for a distribution system which is easily scaleable not only to different column sizes, but also to different individual combinations of packing geometry and packing properties, fluid properties and fluid velocities, and application types. To date, no distribution system is available which meets this end.
As used herein and in the appended claims: the term “fluid system” is intended to designate the apparatus in which liquid is either introduced to or withdrawn from a cell at a zone approximately transverse the direction of flow through the cell. The term “cell” is intended to include the terms “vessel” and “column”, as well as any other structure utilised by practitioners of the separation arts, to effect a separation and/or extraction of components from an admixture by bringing the admixture into contact with solid or liquid exchange media, above referred to as the packing. “Cross-sectional zone” (or region) refers to a region within a cell bounded by cross sections of the cell-oriented transverse (typically approximately normal) the longitudinal direction of flow through the cell. “Longitudinal direction of flow” refers to the direction of flow from an inlet towards an outlet within a cell. “Longitudinal” is used consistently to designate the dominant flow path of fluid through a cell without regard to direction. “Flow connection system” refers to a system of channels or paths that connect two points in a fluid circuit. “Distribution system” refers to structures through which fluids are introduced to a cell and “collection system” refers to structures used to withdraw fluids from a cell, in each instance from a cross-sectional zone.